Ecstasy, the new prescription drug?

What a Long Strange Trip It's Been

Ecstasy, the new prescription drug?

This year, the drug MDMA, otherwise known as ecstasy, could take a step toward medical respectability. Researchers in South Carolina have begun experimenting with MDMA for patients with post-traumatic stress disorder. At Harvard, a long-awaited pilot study will begin on whether the drug can help relieve anxiety and pain in terminal cancer patients in connection with psychotherapy. And studies will also start in Switzerland and Israel, where a former chief psychiatrist of the Israel Defense Forces will oversee work with people whose PTSD stems from terrorism or war.

Ecstasy gained notoriety as a party drug in the 1980s and 1990s. (Recall teenagers at raves with sparkly eyes and pacifiers rolling and dancing all night; a revival appears to be under way in England.) Enthusiasts say the drug makes them feel relaxed, energetic, and mentally clear. One likened it to a six-hour orgasm. In rare cases, however, users died after dancing for hours and overheating, or after taking mixtures of ecstasy and other drugs. Animal studies have shown that long-term, heavy ecstasy use can be risky for the brain. Human studies have found some ill effects in chronic users, as well. The government classifies MDMA (or 3,4-methylenedioxymethamphetamine) along with heroin, LSD, and marijuana as a Schedule 1 drug, which means that it's illegal and has no recognized medical uses.

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But research has not proved that moderate or low doses of ecstasy are particularly dangerous. And avant-garde psychiatrists have long argued that in a controlled clinical setting, low amounts can play a role by reducing fear, without sedation, and so encourage openness and emotional insight. "There is nothing else like this in psychiatry—a fast-acting anti-anxiety medication that makes people alert and talkative," says Julie Holland, a psychiatrist at NYU Medical Center. If available to treat patients, "It would be incredibly useful." Some mental-health professionals interested in exploring MDMA's therapeutic uses protested when the government made it illegal 20 years ago. Stories of the drug's power to combat the psychological effects of terminal illness have continued to surface over the years. But proponents have had little but anecdote to go on. The current wave of studies should bring new rigor to answering an old question: whether MDMA deserves to be a prescription drug.

MDMA was patented more than 90 years ago by the German chemical company E. Merck. For years, it was essentially shelved for reasons that aren't clear. In the 1950s, the U.S. Army conducted research on MDMA, perhaps as a potential incapacitant or truth serum, but apparently dropped the idea. The compound was rediscovered in the late 1970s by chemist and psychedelic cult hero Alexander Shulgin, who synthesized it for recreational use (and supplied it to at least one psychiatrist interested in trying it with patients).

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Ecstasy works by prompting the brain to release a flood of neurotransmitters, including serotonin, which is believed to kick off the sensations of physical pleasure and euphoria. That sounds nice, but animal research suggests that high doses of the drug can cause the nerve endings that release serotonin to degenerate, ultimately lowering its levels in the brain. Some studies suggest that heavy users sustain damage to their serotonin systems. Long-term users may also experience increased anxiety, depression, or sleep disturbances. Recently, researchers in the Netherlands reported preliminary findings to suggest that in new users, low doses of ecstasy can alter blood-flow patterns in the brain and may result in small decreases in verbal memory.

In truth, this litany of harms is not as scary or as conclusive as it sounds, however. The best-known neuroimaging work purporting to show ecstasy-related long-term damage to the human serotonin system was fraught with methodological problems. Much of the research on the drug's apparent psychological or behavioral effects in chronic users fails to account for other drugs, like cocaine or marijuana, which ravers often take, as well. Nor does most research account for other substances like methamphetamine, DXM, and ketamine that pills sold as X may contain.

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John Halpern of Harvard Medical School, who is running the study on MDMA for cancer patients, has tried to avoid this problem by studying a group of ravers in Utah who took large quantities of ecstasy but rarely used other illegal substances or drank alcohol. (Apparently, the mores of this largely Mormon area allowed the ravers to conclude that X isn't as bad as drinking—Halpern isn't sure why.) He found that those who took the drug 60 or more times performed worse on a number of neuropsychological tests, especially those involving mental processing speed and impulsivity. But the heavy users still performed within the normal range. And those who used X fewer than 50 times did not show these effects. When Halpern combined data on all the users, regardless of the extent of their use, he found no significant differences between users and nonusers, including in their scores on memory tests. (The recent Dutch work that links low doses of X to small memory changes is, so far, difficult to evaluate.)

Minor and probably transient memory impairment may not be so bad. And MDMA would be safer in a clinical setting, where the patient's mind-set would be different and the drug's purity guaranteed. So can the anti-anxiety effects of ecstasy be harnessed to good effect under a psychiatrist's care? George Greer, perhaps the best known of the doctors who gave their patients MDMA in the 1980s, prescribed it to about 80 patients who suffered from mild depression, anxiety, or relationship troubles. He says they could more freely remember and discuss difficult events. A few felt tired, depleted, or anxious the next day. But according to Greer, none suffered lasting side effects. Other psychiatrists say that ecstasy has the potential to accelerate therapy and to enhance the therapeutic alliance, creating a closeness that carries over to future sessions. But neither Greer nor anyone else conducted any controlled studies to prove the point.

In the Harvard and South Carolina studies, patients will be screened for physical and psychological conditions that might make MDMA dangerous to them. (High blood pressure and major medical problems are pre-emptive, as are psychoses.) The idea is to look for benefits in psychotherapy, but also to watch out for adverse reactions. The studies include two psychotherapy sessions with the drug and multiple sessions without it, so subjects and their therapists can integrate material stirred up under the influence. Both are designed as randomized, double blind, controlled trials—the gold standard of scientific research. And both have been approved by the Food and Drug Administration.

It's too soon to say what these trials will yield. But if all goes well, MDMA could help some patients, and also help build acceptance for parallel work on the potential therapeutic effects of psilocybin (found in 'shrooms) or even LSD. Even at this late date, it's possible to imagine for psychiatry a small psychedelic renaissance.